Alcohol use, suicidality and virologic non‐suppression among young adults with perinatally acquired HIV in Thailand: a cross‐sectional study

Abstract Introduction Young adults with perinatally acquired HIV (YA‐PHIV) are facing transitions to adult life. This study assessed health risk behaviours (including substance use), mental health, quality of life (QOL) and HIV treatment outcomes of Thai YA‐PHIV. Methods A cross‐sectional study was conducted in Thai YA‐PHIV aged 18–25 years who were enrolled in a prospective cohort study at five tertiary paediatric HIV care centres in Thailand. Study data were obtained through face‐to‐face interviews from November 2020 to July 2021. Assessments were performed for alcohol use (Alcohol Use Disorders Identification Test; AUDIT), smoking (Fagerstrom Test for Nicotine Dependence), drug/substance use (Drug Abuse Screening Test; DAST‐10), depression (Patient Health Questionnaire for Adolescents; PHQ‐A), anxiety (Generalized Anxiety Disorder; GAD‐7) and QOL (World Health Organization QOL Brief‐Thai). HIV treatment outcomes were extracted from the National AIDS Program database. Results Of 355 YA‐PHIV, 163 (46%) were males: their median age was 21.7 (interquartile range, IQR 20.2–23.5) years. There were 203 YA‐PHIV (58%) who reported ever having sex; 141 (40%) were sexually active in the past 6 months, of whom 86 (61%) reported 100% condom use. Overall, 49 (14%) met the criteria for harmful alcohol use; 28 (7.9%) were alcohol dependent. Sixty (17%) were current smokers and 37 (11%) used drugs/substances. The frequency of moderate up to severe symptoms for depression was 18% and for anxiety was 9.7%. Their overall QOL was good in 180 (51%), moderate in 168 (47%) and poor in five (1.4%). There were 49 YA‐PHIV (14%) with CD4 <200 cells/mm3 and 85 (24%) with virologic non‐suppression (HIV‐RNA >200 copies/ml). On multivariate analyses, the highest education at the primary to high school or vocational school levels (adjusted odds ratio [aOR] 2.02, 95% CI 1.40–3.95, p 0.04), harmful alcohol use (aOR 2.48, 95% CI 1.24–4.99, p 0.01), alcohol dependence (aOR 3.54, 95% CI 1.51–8.31, p <0.01) and lifetime suicidal attempt (aOR 2.66, 95% CI 1.11–6.35, p 0.03) were associated with non‐suppression. Conclusions Regular screening for alcohol use and mental health, including suicidality, would be useful to identify YA‐PHIV who need more intensive psychosocial support or referral services to ensure they can achieve and maintain a high QOL into adult life.


I N T R O D U C T I O N
After almost two decades of national scale-up of antiretroviral treatment in Thailand, children with perinatally acquired HIV have grown up into young adults (YA-PHIV). Health risk behaviours increasingly reported among YA-PHIV include the use of alcohol, other substances and tobacco [1,2], which have been associated with reduced adherence and unfavourable treatment outcomes [3]. Mental health problems are also increasing, which can negatively impact antiretroviral treatment (ART) adherence [4][5][6][7][8]. Studies of quality of life (QOL) in YA-PHIV have had mixed results, with some reporting lower [9], unchanged [10] and better QOL [11] compared to HIV-negative youth, depending on the domains assessed.
YA-PHIV additionally have had to face multiple challenges that extended beyond maintaining their physical health, including HIV-related stigma [12] and familial and economic insecurities [13]. The combination of poorer health and social instability has led some YA-PHIV to fall behind in their formal education [14,15], which could negatively impact their ability to function as independent adults in society.
Data on the health risk behaviours, mental health and QOL of Asian YA-PHIV and their association with treatment outcomes would provide valuable insights into how HIV programmes can better target their resources to provide more effective support to YA-PHIV as they age. While most Thai YA-PHIV were transitioned out of paediatric clinics to either adult clinics in the same hospitals or other HIV care facilities around the age of 15 or older following the decentralization policy [16], Thailand's relatively longer history of ART scaleup in the region presents an opportunity to study these outcomes in an older cohort.

Study design and recruitment
We conducted a cross-sectional study at five tertiary paediatric HIV care centres in Bangkok (two sites), Chiang Mai, Chiang Rai and Khon Kaen, Thailand. Inclusion criteria were: (1) aged 18-25 years at enrolment; (2) had perinatally acquired HIV infection; and (3) initiated ART at the paediatric HIV clinic at the study sites before transitioning to an adult clinic, or remained in the paediatric clinics. From November 2020 to July 2021, 811 potential participants who were previously under care at the clinics were identified from existing databases at each participating site. The study team contacted 586 (72%) by approaching them during regular followup care or by making phone calls to those already transferred to other clinics. Due largely to COVID-19 travel restrictions, 355 (61%) YA-PHIV were able to come to a clinic in person to participate in the study. Those with cognitive disabilities or who had active acute illnesses were excluded. The study was approved by the institutional review boards of each study site. Written informed consent was obtained before enrolment.

Data collection and tools
Baseline data at cohort enrolment were used in this analysis. Participant data on the most recent CD4 count and HIV RNA within the past 12 months after enrolment were collected from the National AIDS Program database. Viral non-suppression was defined as having an HIV RNA >200 copies/ml [17]. Data on socio-demographic information and sexual behaviours were collected from participating YA-PHIV by study staff during face-to-face interviews (total 15-20 minutes). They were asked to self-complete six paper-based questionnaires about their health risk behaviours, mental health and QOL.
1) The Alcohol Use Disorders Identification Test (AUDIT) was used to assess alcohol use. Harmful alcohol use was defined as having AUDIT scores ≥8 in both sexes, and alcohol dependence was defined as having AUDIT scores ≥13 in females and ≥15 in males [18,19]. 2) The Drug Abuse Screening Test (DAST-10) was used to assess substance use, excluding alcohol and smoking, in the past 12 months. The degree of problems related to drug abuse was classified by score as low (1-2), moderate (3)(4)(5) and substantial (≥6) [20].

Statistical analysis
Categorical variables are presented as counts and percentages, and continuous variables as medians with interquartile ranges (IQR). Pearson's chi-square test, Fisher's exact test and Z-test were utilized to assess for associations between variables. Factors associated with virologic non-suppression were assessed using univariate and multivariate logistic regression, and presented as odds ratios with a 95% confidence interval (CI) and Z-test p-values. Variables with p <0.1 in the univariate analysis were included in the multivariate analysis. Stata/SE version 13.0 was used for all data analyses.

D I S C U S S I O N
Alcohol use and suicidality were associated with poorer treatment outcomes among Thai YA-PHIV. More than half of study participants used alcohol, reflecting increasing use with age when compared to data on younger adolescents with HIV in the region. A 2014 study in Thailand, Malaysia and Vietnam reported that 32% of adolescents at the median age of 14.5 years drank alcohol [27]. The frequency and severity of alcohol use among Thai YA-PHIV in this study was higher than in a Kenyan study in adolescents and young adults with HIV who were at a similar median age of 21 years [28]. They reported alcohol use among 13%, with 5.4% drinking at harmful and 2.0% at dependent levels. Alcohol use also is subject to other aspects of the local context. While the Thai National survey in 2013 reported prevalence of alcohol use in those 13-24 years was 28% [29], a community-based survey in rural Thailand reported alcohol use among adolescents aged 12-18 years as high as 47% [30]. Nevertheless, the association of harmful or dependent alcohol use with virologic non-suppression in our cohort emphasizes the importance of early intervention among YA-PHIV. The frequency of smokers (17%) in our study was slightly lower than that in general Thai youth aged between 13 and 24 years (23%) [29]. A reduction in the number of smokers has been observed nationwide following years of anti-smoking campaigns in Thailand, while the number of new alcohol drinkers still increased [31,32]. Reports of depression and anxiety among adolescents and YA-PHIV vary by age, geographic context and screening tool used. The 18% and 9.7% prevalences of depressive and anxiety symptoms, respectively, in our study were similar to previous Thai studies that reported 15% depression and 10% anxiety in Bangkok [33]; and 11% depression and 7% anxiety in Chiang Mai [34]. Both studies assessed youth with PHIV at the median age of 19 years. Another study in Northeast Thailand reported depressive disorders in 18% of YA-PHIV (median age 17.5 years) and documented an association with virologic failure [35]. A Chinese study in adolescents with HIV (mean age 16 years) reported a prevalence of depressive symptoms at 32% [36]. Moreover, depressive symptoms were reported among 61% of Kenyan adolescents and young adults with HIV (median age 21 years) [37].
In terms of suicidality, a school-based student health survey in Thailand reported the overall prevalence of suicidal ideation at 8.8% in 2008 [38], which increased to 20.5% in 2015twice the rate found in our study [39]. Nevertheless, having a history of prior suicide attempt was associated with virologic non-suppression, emphasizing the importance of including suicidality assessments in the context of comprehensive mental health screening for YA-PHIV to identify those at risk. The majority of YA-PHIV reported either good or moderate overall QOL. Similar to mental health screening data, studies of the association between QOL and HIV outcomes differed by context and population. A Spanish study in youth with PHIV reported worse QOL using the SF-12 tool across domains of physical and mental health in comparison to HIV-negative youth [40]. In contrast, a Dutch study using the PedSqL tool reported better QOL in youth with PHIV compared to HIV-negative youth in most domains tested [11].
Longitudinal assessment of QOL using the same tool in the same population may be needed for more accurate assessments over time. The virologic suppression rate (76%) in our study compares to reports from the UK (84%) and the United States (60%) [41,42]. The UNAIDS third 90 target remains difficult for YA-PHIV to reach, which supports the need for more attention to this population [43]. While only 61% of sexually active participants used condoms 100% of the time, increased promotion of condom use could minimize the risk of HIV and other sexual-transmitted infection transmission, especially in those who are not virally suppressed. A strength of this study was that it was conducted at multiple sites and contexts in Thailand, increasing our ability to apply our findings more broadly to YA-PHIV nationwide and compare them to other countries in the region. However, limitations included lacking age-matched control groups who were exposed or unexposed to HIV, and socio-demographic and economic data from families during childhood or early adolescence. This prevents us from assessing whether shared environments differentially impacted siblings growing up without HIV. In addition, there was a risk of selection bias, as participants were those who had been retained in care at study sites prior to enrolment, and may consequently have had better health outcomes or less frequent risk behaviours than YA-PHIV who were not in care at all or who returned to care later as adults. There was also a risk of social desirability bias in the self-reported screening results due to the sensitive nature of the topics raised. The study was conducted during the COVID-19 pandemic, which may have affected symptoms and perspectives on mental health and QOL among the YA-PHIV. Due to the cross-sectional design, we could not draw causal inferences between health risk behaviours, mental health and treatment outcomes. Nevertheless, it remains notable that over half of Thai YA-PHIV in our cohort used alcohol, and significant associations between alcohol use, suicidality and virologic non-suppression were observed.  10 from the univariate model were included in the multivariate analysis, employment status was excluded due to collinearity with education. c Two participants with missing HIV RNA and two who did not complete WHO-QOL-BREF were excluded.

C O N C L U S I O N S
Mental health and health risk behaviour screening should be incorporated into routine care for YA-PHIV to identify those who need additional psychiatric assessment and prevention interventions in order for them to maintain HIV disease control and thrive in their communities. Helping them to achieve and sustain the highest possible QOL and other health outcomes should be some of the ultimate goals for HIV care of YA-PHIV.

C O M P E T I N G I N T E R E S T S
The authors have no competing interests.

A U T H O R S ' C O N T R I B U T I O N S
LA, PK, PL, PO, TP and KC: Study design, study conducting, data collection, data cleaning, data interpretation, manuscript preparation and reviewing. SK: Data analysis plan, statistical analysis, manuscript preparation and reviewing.
WNS, TS and SR: Study conducting, data collection, data interpretation and manuscript reviewing.
TS, JLR and AHS: Study design, data collecting plan, sponsor coordination, data interpretation and manuscript reviewing.